Comparative effectiveness of first-line systemic treatments for metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.

OBJECTIVES: No head-to-head trials had been performed to estimate the relative effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). We aimed to perform a systematic review and network meta-analysis to evaluate the comparative effectiveness of various systemic treatment agents for patients with mCRPC. METHODS: A comprehensive literature search was conducted for abstracts and full-text articles from the database's inception through April 27, 2023. The study concentrated on assessing radiographic progression-free survival (rPFS) for both overall and homologous recombination repair mutation (HRRm) population, with overall survival (OS) as the secondary measure. Under the Bayesian framework, the overall effect was pooled using the fixed-effects model in base case analysis. Scenario analysis using restricted mean survival time (RMST) methods was performed to test the robustness of the results. RESULTS: Nine studies with 6,830 patients and 8 unique treatment options were included. Network meta-analysis demonstrated that talazoparib in combination with enzalutamide (TALA + ENZA; overall population, hazard ratio [HR], 0.20; 95% credible interval [CrI]: 0.16-0.26; RMST, 3.51; 95% confidence interval [CI] 2.46-4.60; HRRm population, HR, 0.15; 95% CrI: 0.09-0.23; RMST, 4.14; 95% CI 2.84-5.39) was superior to other treatments in the first-line setting in terms of rPFS. The results of Bayesian framework and RMST models showed consistent efficacy ranks. When extrapolated to overall survival benefit, within the Bayesian framework, olaparib plus abiraterone acetate and prednisone (OLAP + AAP) achieved the highest OS benefit for the overall population, which was not statistically significant when compared to TALA + ENZA. However, TALA + ENZA achieved the highest OS benefit at 3 years by applying RMST. CONCLUSIONS: We suggest that talazoparib in combination with enzalutamide is probably a preferred treatment agent for the overall population and HRRm patients with mCRPC. Given the limitations of network framework and the modeling assumptions undertaken to finalize the analyses, results should be cautiously interpreted.

SEOM clinical guidelines for the treatment of advanced prostate cancer (2020).

The treatment of advanced prostate cancer has evolved due to recent advances in molecular research and new drug development. Dynamic aberrations in the androgen receptor, DNA repair genes, PTEN-PI3K, and other pathways drive the behavior of advanced prostate cancer allowing a better selection of therapies in each patient. Tumor testing for BRCA1 and BRCA2 is recommended for patients with metastatic prostate cancer, also considering a broad panel to guide decisions and genetic counseling. In symptomatic metastatic patients, castration should be stared to palliate symptoms and prolong survival. In high-risk or high-volume metastatic hormone-naïve patients, castration should be combined with docetaxel, abiraterone, enzalutamide or apalutamide. Radiotherapy to the primary tumor combined with systemic therapy is recommended in low-volume mHNPC patients. In patients with non-metastatic castration-resistant tumors, risk stratification can define the frequency of imaging. Adding enzalutamide, darolutamide or apalutamide to these patients prolongs metastasis-free and overall survival, but potential adverse events need to be taken into consideration. The choice of docetaxel, abiraterone or enzalutamide for treating metastatic castration-resistant patients depends on previous therapies, with cabazitaxel being also recommended after docetaxel. Olaparib is recommended in BRCA1/BRCA2 mutated castration-resistant patients after progression on at least one new hormonal therapy. Aggressive variants of prostate cancer respond to platinum-based chemotherapy. To optimize treatment efficiency, oncologists should incorporate all of these advances into an overall therapeutic strategy.

Risk of fatigue and anemia in patients with advanced cancer treated with olaparib: A meta-analysis of randomized controlled trials.

INTRODUCTION: PARP inhibitors are a new class of drugs that are currently being studied in several malignancies. Olaparib is FDA-approved for advanced breast cancer and advanced ovarian cancer patients. Fatigue and anemia are among the most common cancer and treatment-related symptoms. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) to characterize the incidence and relative risks (RRs) of fatigue and anemia associated with olaparib. METHODS: PubMed, Cohrane, Embase and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018. The eligible studies were phase II and III RCT of olaparib. Safety profile from each selected study was evaluated for all-grade and high-grade fatigue and anemia adverse events. Summary incidences and the RR, with 95% confidence intervals, of all-grade and high-grade events were calculated using random-effects or fixed-effects model based on the heterogeneity of selected studies. RESULTS: A total of 9 trials were selected, and included 2074 patients with advanced ovarian, gastric, prostate, lung or breast cancer. 908 patients received placebo/control treatments and 1166 received olaparib alone or combination with other active cancer treatments. The RR of all-grade and high fatigue was 1.24 (95% CI, 1.10-1.39) and 1.71 (95% CI, 1.06-2.77), respectively. The RR of all-grade and high-grade anemia was 2.10 (95% CI, 1.48-2.98) and 3.15 (95% CI, 1.73-5.71), respectively. CONCLUSION: Our findings suggest that the olaparib treatment is associated with an increased risk of fatigue and anemia. Since fatigue and anemia are very common treatment related adverse events, and both can impair the quality of life of patients, it is important to identify them early and manage it accordingly in order to optimize the overall treatment.

Comparaçäo da eficácia e tolerabilidade da azelastina spray nasal e loratadina em pacientes com rinite alérgica perene / A comparison of eficacy and tolerability of azelastine nasal spray and loratadine in patients with perennial allergic rhinits

Cinquenta e seis pacientes com rinite alérgica perene foram tratados por duas semanas, em estudo duplo-cego, duplo-placebo, randomizado, comparando azelastina spray nasal (0,14 mg/narina duas vezes ao dia) e loratadina comprimidos (10 mg uma vez ao dia). Os sintomas avaliados foram espirros, prurido nasal, rinorréia, edema da mucosa nasal, obstruçäo nasal, tosse, alteraçöes do olfato, prurido ocular, vermelhidäo conjuntival, lacrimejamento, fotofobia, vermelhidäo da mucosa faríngea e prurido faríngeo. Estes sintomas da rinite foram avaliados pelo investigador de acordo com uma escala de quatro pontos (0 = ausente, 1 =leve, 2 = moderado, 3 = severo), antes do tratamento, uma e duas semanas após seu início. Espirros, obstruçäo nasal, prurido nasal e rinorréia foram avaliados diariamente pelos pacientes de acordo com a mesma escala. Ao final da primeira e da segunda semanas de tratamento uma avaliaçäo global da resposta terapêutica e da tolerabilidade foi feita pelos pacientes e pelo investigador. Em comparaçäo com a avaliaçäo pré-tratamento, verificou-se uma reduçäo da pontuaçäo de cada um dos sintomas em ambas as avaliaçöes, tanto para os pacientes que receberam azelastina quanto para os que receberam loratadina. Com exceçäo da rinorréia, cuja melhora foi significantemente superior no grupo azelastina, näo foram observadas diferenças estatisticamente significativas entre os dois grupos. Concluindo, a azelastina mostrou-se ser täo eficaz quanto a loratadina no alívio dos sintomas da rinite alérgica perene

Comparaçäo da eficácia e tolerabilidade da azelastina spray nasal e loratadina comprimidos em pacientes com rinite alérgica perene / A comparison of efficacy and tolerability of azelastine nasal spray and loratadine tablets in patients with perennial allergic rhinitis

Cinquenta e seis pacientes com rinite alérgica perene foram tratados por duas semanas em um estudo duplo-cego, "double-dummy", randomizado, comparando azelastina spray nasal (0,14 mg/narina, duas vezes ao dia) e loratadina comprimidos (10 mg, uma vez ao dia). Os sintomas avaliados foram espirros, prurido nasal, rinorréia, edema da mucosa nasal, obstruçäo nasal, tosse, alteraçöes do olfato, prurido ocular, vermelhidäo conjuntival, lacrimejamento, fotofobia, vermelhidäo da mucosa faríngea e prurido faríngeo. Estes sintomas da rinite foram avaliados pelo investigador, de acordo com uma escala de quatro pontos (0 = ausente, 1 = leve, 2 = moderado, 3 = severo), antes do tratamento, uma e duas semanas após seu início. Espirros, obstruçäo nasal, prurido nasal e rinorréia foram avaliados diariamente pelos pacientes de acordo com a mesma escala. Ao final da primeira e da segunda semanas de tratamento uma avaliaçäo global da resposta terapêutica e da tolerabilidade foi feita pelos pacientes e pelo investigador. Comparado à avaliaçäo pré-tratamento, verificou-se uma reduçäo da pontuaçao de cada um dos sintomas em ambas as avaliaçöes, tanto para os pacientes que receberam azelastina como para os que receberam loratadina. Näo foram observadas diferenças estatisticamente significantes entre os dois grupos. Concluindo, a azelastina mostrou-se ser täo eficaz quanto a loratadina no alívio dos sintomas da rinite alérgica perene.

Azelastina spray nasal no tratamento da rinite alérgica perene: estudo multicêntrico brasileiro / Azelastine nasal spray in the treatment of perennial allergic rhinitis: a Brazilian multicentric study

Neste estudo multicêntrico, aberto, prospectivo, antes-após tratamento e nao comparativo, foi avaliada a resposta, de 313 pacientes portadores de rinite alérgica perene, ao uso de azelastina spray nasal, na dose de 0.14 mg em cada narina duas vezes ao dia por 14 dias. A íntensidade da doença foi constatada através da graduaçao dos sinais e sintomas nasais, conforme escore de 4 pontos (O,1,2,3), tendo participado do estudo aqueles que apresentavam um escore maior ou igual a 8. No terceiro, sétimo e décimo-quarto dia, o paciente era novamente avaliado. Já no 3( dia de tratamento os sintomas como espirros, prurido nasal, rinorréia e obstruçao mostraram uma reduçao significante da média dos escores (p< O,0001). O edema da mucosa nasal regrediu significantemente (p